反应详情

温度

-40 °C

400 ml of toluene is charged into a round-bottom flask, which is cooled to −40° C. and then solution of n-butyllithium (76.6 g) in hexane is added and the temperature of the reaction mixture is maintained at −40° to −50° C. 2-Bromopyridine (189.2 g) is then added to the reaction mixture and the temperature is maintained at −65° to −55° C. for 35 to 45 minutes. 200 g of 4′-methyl-3-pyrrolidinopropiophenone in 200 ml of toluene is added to the reaction mixture in the R.B. flask. The reaction mass is stirred at −65° to −55° C. for 2 hours and it is further stirred for 1 hour at −40° to −50° C. The reaction mass is quenched in ice water and HCl is added slowly at 10° to 20° C. to get a clear solution. The aqueous layer is separated and it is added slowly to NaOH in the R.B. flask at 15° C.-20° C. The reaction mass is stirred for half an hour and the precipitated solid is filtered off. The solid is transferred into a round-bottom flask and then 500 ml of methanol is added. The reaction mass is refluxed at 60° C. for half an hour and the mass is cooled to 10°-20° C. The solid mass is filtered and dried under suction for one hour. On drying the solid compound at 70°-80° C. for 4 hours, 1-(4-methylphenyl)-1-(2-pyridyl)-3-pyrrolidinopropan-1-ol (220 g, 80.5% yield) with 99.3% HPLC purity is obtained whose melting point is in the range of 115°-119° C.

1. temperaturethe temperature of the reaction mixture is maintained at −40° to −50° C
2. temperaturethe temperature is maintained at −65° to −55° C. for 35 to 45 minutes
3. stirringit is further stirred for 1 hour at −40° to −50° C
4. customThe reaction mass is quenched in ice water
5. additionHCl is added slowly at 10° to 20° C.
6. customto get a clear solution
7. customThe aqueous layer is separated
8. additionit is added slowly to NaOH in the R.B
9. customat 15° C.-20° C
10. stirringThe reaction mass is stirred for half an hour
11. filtrationthe precipitated solid is filtered off
12. customThe solid is transferred into a round-bottom flask
13. addition500 ml of methanol is added
14. temperatureThe reaction mass is refluxed at 60° C. for half an hour
15. temperaturethe mass is cooled to 10°-20° C
16. filtrationThe solid mass is filtered
17. customdried under suction for one hour
18. customOn drying the solid compound at 70°-80° C. for 4 hours